A Phase 3 Study to Evaluate the Efficacy of Lifitegrast in Subjects With Dry Eye

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT01743729
Collaborator
(none)
720
31
2
9.8
23.2
2.4

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of lifitegrast ophthalmic solution compared to placebo in the treatment of dry eye.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
720 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy of a 5.0% Concentration of Lifitegrast Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Currently Using Artificial Tears (OPUS-2)
Actual Study Start Date :
Dec 7, 2012
Actual Primary Completion Date :
Oct 1, 2013
Actual Study Completion Date :
Oct 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lifitegrast

Lifitegrast Ophthalmic Solution (5.0%)

Drug: Lifitegrast
Lifitegrast Ophthalmic Solution 5.0%
Other Names:
  • SAR 1118
  • Placebo Comparator: Placebo

    Drug: Placebo
    Placebo for Lifitegrast Ophthalmic Solution 5.0%

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 [Baseline to Day 84]

      Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.

    2. Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 [Baseline to Day 84]

      Eye dryness score was assessed on a visual analogue scale (a 7-item [burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Willing and able to read, sign and date the informed consent and HIPAA documents

    • Willing and able to comply with all study procedures

    • Be at least 18 years of age

    • Patient-reported history of dry eye in both eyes

    • A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period

    • Artificial tear use within the past 30 days

    Exclusion Criteria:
    • Any ocular condition that, in the opinion of the Investigator, could affect study parameters including, but not limited to, active ocular infection, ocular inflammation, glaucoma, and/or diabetic retinopathy

    • Unwilling to avoid wearing contact lenses for 7 days prior to first visit and for the duration of the study

    • Any blood donation or significant loss of blood within 56 days of Visit 1

    • Any history of immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant.

    • Use of any prohibited medications at any time during the study unless otherwise specified

    • Any significant illness that could interfere with study parameters

    • History of laser assisted in situ keratomileusis (LASIK) or similar type of corneal refractive surgery within 12 months prior to first visit, and/or any other ocular surgical procedure within 12 months prior to first visit; or any scheduled ocular surgical procedure during the study period.

    • Known history of alcohol and/or drug abuse

    • Subjects with Dry eye secondary to scarring or destruction of conjunctival goblet cells (as with Vitamin A deficiency)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 OPUS-2 Investigational Site Artesia California United States 90701
    2 OPUS-2 Investigational Site Hemet California United States 92545
    3 OPUS-2 Investigational Site Lancaster California United States 93534
    4 OPUS-2 Investigational Site Mission Hills California United States 91345
    5 OPUS-2 Investigational Site Montebello California United States 90640
    6 OPUS-2 Investigational Site Newport Beach California United States 92663
    7 OPUS-2 Investigational Site Petaluma California United States 94954
    8 OPUS-2 Investigational SIte Rancho Cordova California United States 95670
    9 OPUS-2 Investigational Site Danbury Connecticut United States 06810
    10 OPUS-2 Investigational Site Fort Myers Florida United States 33901
    11 OPUS-2 Investigational Site Hoffman Estates Illinois United States 60169
    12 OPUS-2 Investigational Site Indianapolis Indiana United States 46260
    13 OPUS-2 Investigational Site New Albany Indiana United States 47150
    14 OPUS-2 Investigational Site Lexington Kentucky United States 40509
    15 OPUS-2 Investigational Site Saint Paul Minnesota United States 55082
    16 OPUS-2 Investigational Site Chesterfield Missouri United States 63017
    17 OPUS-2 Investigational Site Des Peres Missouri United States 63131
    18 OPUS-2 Investigational Site Independence Missouri United States 64055
    19 OPUS-2 Investigational Site Kansas City Missouri United States 64111
    20 OPUS-2 Investigational Site Washington Missouri United States 63090
    21 OPUS-2 Investigational Site New York New York United States 10016
    22 OPUS-2 Investigational Site New York New York United States 10036
    23 OPUS-2 Investigational Site Wantagh New York United States 11793
    24 OPUS-2 Investigational Site Cleveland Ohio United States 44115
    25 OPUS-2 Investigational Site Philadelphia Pennsylvania United States 19148
    26 OPUS-2 Investigational Site Houston Texas United States 77034
    27 OPUS-2 Investigational Site Houston Texas United States 77055
    28 OPUS-2 Investigational Site League City Texas United States 77573
    29 OPUS-2 Investigational Site San Antonio Texas United States 78209
    30 OPUS-2 Investigational Site San Antonio Texas United States 78229
    31 OPUS-2 Investigational Site Norfolk Virginia United States 23502

    Sponsors and Collaborators

    • Shire

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT01743729
    Other Study ID Numbers:
    • 1118-DRY-300
    First Posted:
    Dec 6, 2012
    Last Update Posted:
    Jun 23, 2021
    Last Verified:
    Jun 1, 2021
    Keywords provided by Shire
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Two of 720 participants were excluded from data analysis due to duplication. Therefore, 718 participants were randomized and treated. One participant from placebo arm (N=360) has taken study drug by mistake and considered for "Lifitegrast" arm (N=358). Therefore, Placebo (N=359), Lifitegrast (N=359) were considered for safety analysis.
    Arm/Group Title Lifitegrast Placebo
    Arm/Group Description
    Period Title: Overall Study
    STARTED 358 360
    COMPLETED 321 348
    NOT COMPLETED 37 12

    Baseline Characteristics

    Arm/Group Title Lifitegrast Placebo Total
    Arm/Group Description Total of all reporting groups
    Overall Participants 358 360 718
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.7
    (13.93)
    58.9
    (14.26)
    58.8
    (14.09)
    Sex: Female, Male (Count of Participants)
    Female
    285
    79.6%
    265
    73.6%
    550
    76.6%
    Male
    73
    20.4%
    95
    26.4%
    168
    23.4%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84
    Description Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.
    Time Frame Baseline to Day 84

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) set included all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Lifitegrast Placebo
    Arm/Group Description
    Measure Participants 358 360
    Baseline
    2.39
    (0.763)
    2.40
    (0.722)
    Change from Baseline to Day 84
    -0.73
    (0.926)
    -0.71
    (0.943)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lifitegrast, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6186
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Treatment Effect
    Estimated Value 0.03
    Confidence Interval (2-Sided) 95%
    -0.10 to 0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84
    Description Eye dryness score was assessed on a visual analogue scale (a 7-item [burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome.
    Time Frame Baseline to Day 84

    Outcome Measure Data

    Analysis Population Description
    ITT population with last observation carried forward (LOCF).
    Arm/Group Title Lifitegrast Placebo
    Arm/Group Description
    Measure Participants 358 360
    Baseline
    69.68
    (16.954)
    69.22
    (16.761)
    Change from Baseline to Day 84
    -35.30
    (28.400)
    -22.75
    (28.600)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lifitegrast, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Treatment Effect
    Estimated Value 12.61
    Confidence Interval (2-Sided) 95%
    8.51 to 16.70
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description One participant from placebo group (N=360) has taken study drug by mistake and considered for "Lifitegrast" group (N=358). Therefore, Placebo (N)= 359, Lifitegrast (N)=359 were considered for safety analysis.
    Arm/Group Title Lifitegrast Placebo
    Arm/Group Description
    All Cause Mortality
    Lifitegrast Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Lifitegrast Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/359 (0.8%) 4/359 (1.1%)
    Ear and labyrinth disorders
    Vertigo 1/359 (0.3%) 1 0/359 (0%) 0
    Endocrine disorders
    Thyrotoxic crisis 1/359 (0.3%) 1 0/359 (0%) 0
    Gastrointestinal disorders
    Colitis ischaemic 0/359 (0%) 0 1/359 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 0/359 (0%) 0 1/359 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer 0/359 (0%) 0 1/359 (0.3%) 1
    Renal cancer 1/359 (0.3%) 1 0/359 (0%) 0
    Nervous system disorders
    Cerebrovascular accident 0/359 (0%) 0 1/359 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    Lifitegrast Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 102/359 (28.4%) 30/359 (8.4%)
    Eye disorders
    Visual acuity reduced 18/359 (5%) 23 23/359 (6.4%) 28
    General disorders
    Instillation site irritation 28/359 (7.8%) 29 5/359 (1.4%) 5
    Instillation site reaction 25/359 (7%) 29 4/359 (1.1%) 4
    Nervous system disorders
    Dysgeusia 58/359 (16.2%) 58 1/359 (0.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If a multicentre publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicentre Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

    Results Point of Contact

    Name/Title Study Director
    Organization Shire (Note: Lifitegrast was divested to Novartis in 2019)
    Phone +1 866 842 5335
    Email ClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT01743729
    Other Study ID Numbers:
    • 1118-DRY-300
    First Posted:
    Dec 6, 2012
    Last Update Posted:
    Jun 23, 2021
    Last Verified:
    Jun 1, 2021